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© European Medicines Agency, 2022. Reproduction is authorised provided the source is acknowledged.
GCP Inspection Report XXX at XXX site On behalf of the European Medicines Agency
XXX
Inspector in charge of this inspection report
Name:
Position:
Address:
Tel:
E-mail:
XXX XXX XXX
Inspection report date: DD-MM-YYYY
Responses to inspection report: Dated as per Addendum 1
Evaluation of inspection responses: Dated as per Addendum 2
This inspection report may only be reproduced in its entirety and must not be circulated or published without the
European Medicines Agency’s consent, nor may any additions be made to the report.
GCP Inspection Report XXX at XXX site EMA/77942/2017 Report Body Page 2 of 12
Table of contents
1. Administrative information ................................................................................................ 5
2. Background and general information ................................................................................. 6 2.1. Reason and cause for the inspection .................................................................................... 6 2.2. Reference texts ................................................................................................................ 6 2.3. Grading of findings ........................................................................................................... 6 2.4. List of persons involved in the trial and contacted during the inspection ................................... 7
3. Operational resources ........................................................................................................ 8 3.1. Organisation .................................................................................................................... 8 3.2. Personnel ........................................................................................................................ 8 3.3. Qualifications and training ................................................................................................. 8 3.4. Facilities ......................................................................................................................... 8 3.5. Equipment ....................................................................................................................... 8 3.6. Computer systems............................................................................................................ 8
4. Administrative aspects of the trial ..................................................................................... 8 4.1. National competent authority ............................................................................................. 8 4.2. Independent research ethics committee (IEC) ...................................................................... 8 4.3. Other committees, any other validation or authorisations required ........................................... 8 4.4. Contract(s) and agreement(s) ............................................................................................ 8 4.5. Insurance ........................................................................................................................ 8
5. Trial master file .................................................................................................................. 9 5.1. Production, version control and content of essential documents ............................................... 9 5.2. Completeness, availability, content and structure of TMF/ISF .................................................. 9
6. Clinical conduct of the trial ................................................................................................ 9
7. Management of the trial by sponsor/CRO .......................................................................... 9
8. Safety reporting ................................................................................................................. 9
9. Investigational medicinal product(s) (IMPs)/pharmacy .................................................... 9
10. Clinical data management ................................................................................................ 9
11. Source data review/verification ....................................................................................... 9
12. Clinical trial monitoring .................................................................................................... 9
13. Instrument-based diagnostics/ examinations ................................................................. 9
14. Clinical sample management ............................................................................................ 9 14.1. Clinical samples (at investigator site)................................................................................. 9 14.2. Clinical samples (at laboratory or analytical site) ................................................................. 9
15. Laboratory ..................................................................................................................... 10
16. Bioanalysis (PK) laboratory ........................................................................................... 10 16.1. Methods used ............................................................................................................... 10 16.2. Method validation and report .......................................................................................... 10 16.3. Results ........................................................................................................................ 10
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17. Pharmacokinetic analysis ............................................................................................... 10
18. Statistical analysis ......................................................................................................... 10
19. Reports .......................................................................................................................... 10 19.1. Clinical study report ...................................................................................................... 10 19.2. Bioanalytical report ....................................................................................................... 10
20. Quality management system .......................................................................................... 10 20.1. Standard operating procedures (SOPs) ............................................................................ 10 20.2. Quality control ............................................................................................................. 10 20.3. Quality assurance ......................................................................................................... 10
21. Summary, discussion and conclusion ............................................................................. 11 21.1. Summary and discussion ............................................................................................... 11 21.2. Interim conclusion ........................................................................................................ 11
22. Signatures ...................................................................................................................... 12
Appendices ............................................................................................................................ 1 A1. Summary of activities inspected .......................................................................................... 1 A2. Trial documentation and approvals ...................................................................................... 9 A3. Appendix – landscape format. ....................................................................................... 10 A4. Title .............................................................................................................................. 11
GCP Inspection Report XXX at XXX site EMA/77942/2017 Report Body Page 4 of 12
Abbreviations ADR adverse drug reaction
AE adverse event
CA competent authority
CAPA corrective action preventive action
CHMP Committee for Medicinal Products for Human Use
CRA clinical research associate
(e)CRF (electronic) case report form
CRO contract research organisation
CSR clinical study report
CSV computer system validation
DSUR development safety update report
e-Pro electronic patient reported outcome
I inspector
IB investigator’s brochure
ICF informed consent form
ICH International Conference on Harmonisation
(I)EC (independent) ethics committee
IMP investigational medicinal product
IR inspection report
IRT interactive response technologies
ISF investigator site file/investigator TMF
ITT intent-to-treat
IVRS interactive voice response system
IWRS interactive web response system
LI lead inspector
MAA marketing authorisation application
MVR monitoring visit report
PI principal investigator
PIS patient information sheet
PP protocol population
RI reporting inspector
SI sub investigator
QA quality assurance
QC quality control
RA regulatory authority
SAE serious adverse event
SAR serious adverse reaction
SOP standard operating procedure
SUSAR suspected unexpected serious adverse reaction
TMF trial master file
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1. Administrative information
Investigational medicinal product(s)
Product(s)
Application
EMA reference number Name and full address of the applicant
Clinical trial(s)
EudraCT number Sponsor Trial protocol code Trial protocol title Total number of investigator sites Total number of subjects Clinical trial report date and version
Site details
Organisation name Principal investigator [if applicable] Address
Key data from site inspected
Number of subjects at this site First patient first visit Last patient last visit Screened Randomised
Withdrawals/drop outs
Dates of inspection
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Inspection team Authority Country
Reporting inspector (RI)
Lead inspector (LI) XXX
Inspector (I)
Expert
Observer
2. Background and general information
2.1. Reason and cause for the inspection
Text
2.2. Reference texts
• Regulation (EC) 726/2004
• Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001
• Directive 2001/83/EC as amended by Directive 2003/63/EC of 25 June 2003
• Directive 2005/28/EC of the European Commission of 8 April 2005
• CPMP/ICH/135/95 ‘Note for Guidance on Good Clinical Practice’, July 1996
• World Medical Association Declaration of Helsinki, in the version,
• GMP, Annex 13 Manufactur of the investigational medicinal products,
• CPMP/ICH/137/95 “Note for Guidance on Structure and Content of Clinical Study Reports”, July 1996
• CPMP/ICH/363/96 “Note for Guidance on Statistical Principles for Clinical Trials”, September 1998
• CPMP/EWP/QWP/1401/98, Guideline on the Investigation of Bioequivalence’, 1 August 2010
• EMA/CHMP/EWP/192217/2009 ‘Guideline on Bioanalytical Method Validation’, 1 February 2012
2.3. Grading of findings
Critical (CR)
Definition Conditions, practices or processes that adversely affect the rights, safety or wellbeing of the subjects and/or the quality and integrity of data. Critical observations are considered totally unacceptable.
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Critical (CR)
Possible consequences Rejection of data and/or legal action required. Remark Observation classified as critical may include a
pattern of deviations classified as major, bad quality of the data and/or absence of source documents. Manipulation and intentional misrepresentation of data belong to this group.
Major (MA)
Definition Conditions, practices or processes that might adversely affect the rights, safety or wellbeing of the subjects and/or the quality and integrity of data. Major observations are serious deficiencies and are direct violations of GCP principles.
Possible consequences Data may be rejected and/or legal action required.
Remark Observations classified as major, may include a pattern of deviations and/or numerous minor observations.
Minor (MI)
Definition Conditions, practices or processes that would not be expected to adversely affect the rights, safety or wellbeing of the subjects and/or the quality and integrity of data.
Possible consequences Observations classified as minor, indicate the need for improvement of conditions, practices and processes.
Remark Many minor observations might indicate a bad quality and the sum might be equal to a major finding with its consequences.
Comments The observations might lead to suggestions on
how to improve quality or reduce the potential for a deviation to occur in the future.
Responsibility for the finding
The responsibility for addressing the finding will be stated. This could be sponsor/CRO, investigator, IEC etc.
2.4. List of persons involved in the trial and contacted during the inspection
Type here
GCP Inspection Report XXX at XXX site EMA/77942/2017 Report Body Page 8 of 12
Full name Job title Role in the trial inspected
3. Operational resources
3.1. Organisation
Not applicable.
3.2. Personnel
Not applicable.
3.3. Qualifications and training
Not applicable.
3.4. Facilities
Not applicable.
3.5. Equipment
Not applicable.
3.6. Computer systems
Not applicable.
4. Administrative aspects of the trial
Not applicable.
4.1. National competent authority
Not applicable.
4.2. Independent research ethics committee (IEC)
Not applicable.
4.3. Other committees, any other validation or authorisations required
Not applicable.
4.4. Contract(s) and agreement(s)
Not applicable.
4.5. Insurance
Not applicable.
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5. Trial master file
5.1. Production, version control and content of essential documents
Not applicable.
5.2. Completeness, availability, content and structure of TMF/ISF
Not applicable.
6. Clinical conduct of the trial
Not applicable.
7. Management of the trial by sponsor/CRO
Not applicable.
8. Safety reporting
Not applicable.
9. Investigational medicinal product(s) (IMPs)/pharmacy
Not applicable.
10. Clinical data management Not applicable.
11. Source data review/verification
Not applicable.
12. Clinical trial monitoring
Not applicable.
13. Instrument-based diagnostics/ examinations
Not applicable.
14. Clinical sample management
14.1. Clinical samples (at investigator site)
Not applicable.
14.2. Clinical samples (at laboratory or analytical site)
Not applicable.
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15. Laboratory
Not applicable.
16. Bioanalysis (PK) laboratory
16.1. Methods used
Not applicable.
16.2. Method validation and report
Not applicable.
16.3. Results
Not applicable.
17. Pharmacokinetic analysis
Not applicable.
18. Statistical analysis
Not applicable.
19. Reports
19.1. Clinical study report
Not applicable.
19.2. Bioanalytical report
Not applicable.
20. Quality management system
20.1. Standard operating procedures (SOPs)
Not applicable.
20.2. Quality control
Not applicable.
20.3. Quality assurance
Not applicable.
GCP Inspection Report XXX at XXX site EMA/77942/2017 Report Body Page 11 of 12
21. Summary, discussion and conclusion
21.1. Summary and discussion
Type here
21.2. Interim conclusion
Type here
GCP Inspection Report XXX at XXX site EMA/77942/2017 Report Body Page 12 of 12
22. Signatures
Date
Print name
Function
Signature
Date
Print name
Function
Signature
Date
Print name
Function
Signature
GCP INSPECTION REPORT XXX at XXX site EMA/13824/2017 Report Appendices : Page 1/ XX [insert nu
Appendices
A1. Summary of activities inspected
Area [report section]
Reviewed / inspected
(tick*)
Comments Findings
(enter number of)
Operational resources [3] Critical: Major:
OP
TIO
NA
L T
O C
OM
PLE
TE
Organisational structure [3.1]
Interviews with key personnel involved in the trial [3.2]
Delegation of duties & specimen signatures [3.2]
Qualifications, protocol and GCP training of personnel [3.3]
Clinical facilities [3.4]
Laboratory facilities [3.4]
Apparatus, equipment, material, reagents, calibration [3.5]
Archiving facilities [3.4]
Computer systems [3.6] Other (specify)
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Administrative aspects of the trial [4] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
CA approval (initial & amendments) /communication [4.1]
IRB/IEC opinions (initial & amendments) /communication [4.2] Institutional correspondence and approval & other bodies giving approval [4.3]
Contract(s) & agreement(s) [4.4]
Insurance [4.5] Other (specify)
Trial master file (sponsor and investigator) [5] Critical: Major:
OP
TIO
NA
L T
O C
OM
PLE
TE
Production, version control and content of essential documents [5.1] for example:- • PIS/ICF • Protocol & amendments • Investigator brochure • Case report form • Trial manuals/plans/guides (sponsor created) • Instructions/proformas etc. (site created) • Subject screening and enrolment log
Completeness, availability, content and structure of TMF/ISF [5.2], for example:- • Access and storage of essential documents
Other (specify)
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Clinical conduct of the trial [6] Critical: Major: O
PTI
ON
AL
TO
CO
MP
LETE
Subject recruitment
Subject identification
Subject confidentiality
Informed consent process and completed documentation
Subject screening and eligibility Compliance with trial protocol clinical procedures (examinations/assessments)
Other (specify)
Management of the trial by the sponsor/CRO [7] Critical: Major:
OP
TIO
NA
L T
O C
OM
PLE
TE
Delegation of duties
Management of CROs/vendors, if applicable
Trial management, communication, escalation
Investigator selection
Training of investigator sites
Protocol deviation management
Protocol amendment implementation
Serious breaches and issue resolution
Data monitoring and other trial committees Other (specify)
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Safety reporting [8] Critical: Major: O
PTI
ON
AL
TO
CO
MP
LETE
Collection of AES and review
Collection of SAEs
Processing of SAE cases & use of PV databases
Expedited reporting to IEC/CA
Reporting safety information to investigators
Aggregate reports (DSURS)
Urgent safety measures Other (specify)
Investigational medicinal product(s)/pharmacy [9] Critical: Major:
OP
TIO
NA
L T
O C
OM
PLE
TE
Manufacturing/assembly/labelling/importation/QP certification/reconstitution
IMP expiry and extensions
Randomisation implementation
Regulatory green light, shipping and transit
Storage (and temperature monitoring)
IRT system (trial specific build, use)
Prescribing, dispensing and administration to subjects
Subject compliance Accountability (shipping, site and subject level), returns/destruction
Emergency code breaking system Other (specify)
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Clinical data management [10] Critical: Major: O
PTI
ON
AL
TO
CO
MP
LETE
CRF and trial specific eCRF design/build, functionality, source in CRF, (independent copy on site etc.)
Diaries and e-PRO Data entry, verification/validation (edit checks), self-evident corrections, audit trails
Data handling/transfers, coding
Data reconciliation (e.g. with lab data, PV data)
Database lock
Un-blinding Other (specify)
Source data review/verification [11] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Safety & efficacy data (reliability of data, protocol compliance) SDV performed for subject numbers (enter details):
Other (specify)
Clinical trial monitoring [12] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Compliance with monitoring plan/procedures
Reporting of monitoring visits (assessment/routine/close out)
Issue resolution and escalation of issues
Central monitoring activities Other (specify)
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Instrument-based diagnostics/examinations [13] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Laboratories, technical departments, other vendors
Data transfers
Standardisation/validation
Committees involved in evaluations Other (specify)
Clinical sample management [14] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Handling of samples at investigator site (sample taking and management in the clinic) [14.1]
Storage of samples (temperature monitoring)
Handling of samples at laboratory or analytical site [14.2] Other (specify)
Laboratory (not PK – i.e. for biochemistry, haematology etc.) [15] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Certification/accreditation
Normal ranges
Results reporting back to site Other (specify in comments)
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Bioanalysis (PK) laboratory [16] Critical: Major:
OP
TIO
NA
L TO
C
OM
PLE
TE Methods used [16.1]
Method validation and report [16.2]
Results [16.3] Other (specify)
Pharmacokinetic analysis [17] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Statistical/pharmacokinetic software
Incurred sample reanalysis (ISR)
PK profile parameters
Subject populations Other (specify)
Statistical analysis [18] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Trial design input, sample size calculation
Randomisation generation
SAP/TFL shells
Analysis populations & data review meeting
Programming & CSV
Analysis Other (specify)
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Reports [19] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Bioanalytical report [19.1] Same as report
CSR production [19.2] • Content & structure • Management of protocol non compliance • Statement about GCP compliance • Accuracy and completeness
Other (specify)
Quality management system [20] Critical: Major:
OP
TIO
NA
L T
O
CO
MP
LETE
Standard operating procedures [20.1]
Quality control [20.2]
Quality assurance /auditing [20.3] Other (specify)
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A2. Trial documentation and approvals
APPROVAL DATES DOCUMENT VERSIONS
SUBMISSON Substantial (S)/
Non-substantial
(NS)
CA IEC/
IRB
Sponsor
approval
(if applicable)
Investigator
approval
(if applicable)
Any other
required
approvals
Protocol
version
Subject
information and
consent form
version/date
Other
documents
INITIATION/
IMPLEMENTATION
DATE
Initial
Date:
#2
Date:
#3
Date:
#4
Date:
#5
Date:
#6
Date:
#7
Date:
#8
Date:
#9
Date:
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A3. Appendix – landscape format
GCP INSPECTION REPORT XXX at XXX site EMA/13824/2017 Report Appendices : Page 11/ XX [insert number of pages in appendix]
A4. Title
GCP INSPECTION REPORT XXX at XXX site Addendum 1 (Inspection responses) EMA/13824/2017
GCP INSPECTION REPORT XXX at XXX site.
Addendum 1: Response from the sponsor or inspectee
XXX XXX XXX
Date responses received by the inspector: DD/MM/YYYY
The following attached documentation is the response received from the sponsor or inspectee.
GCP INSPECTION REPORT XXX at XXX site.
Addendum 2: Evaluation by the inspectors of the response to the inspection report
XXX XXX XXX
Date of Evaluation: DD/MM/YYYY
Final conclusions from inspection findings
Assessment of the relevance of the findings for the full trial
Type here
Quality of the data and GCP compliance
Type here
Recommendation for the acceptability of the clinical trial data
Type here
GCP INSPECTION REPORT XXX at XXX site Addendum 1 (Inspection responses) EMA/13824/2017
Recommendations for follow up actions (GCP systems)
Type here